Androgen deficiency is known to cause both osteoporosis and sarcopenia. Myokines, humoral factors secreted from the skeletal muscles, have recently been getting attention as the key factors related to the interactions between muscle and bone. Dickkopf (Dkk) 2 is known as an inhibitor of canonical Wnt/β-catenin signaling, and Wnt/β-catenin signaling is crucial for the maintenance of muscle and bone. The present study was therefore performed to investigate the roles of Dkk2 in the alterations of muscle and bone of androgen-deficient mice with orchidectomy (ORX). ORX significantly enhanced Dkk2 mRNA levels, but not other Dkks and secreted frizzled related proteins, in the soleus muscles of mice. Moreover, ORX enhanced serum Dkk2 levels, but not Dkk2 mRNA levels in the tibial bone tissues, the white adipose tissues and liver of mice. In simple regression analyses, serum Dkk2 levels were negatively related to trabecular bone mineral density at the tibias in mice employed in the experiments. In vitro experiments, testosterone suppressed Dkk2 mRNA levels in mouse muscle C2C12 cells. In conclusion, we showed that androgen deficiency enhances Dkk2 expression and secretion in the muscles of mice. Dkk2 might be involved in androgen deficiency-induced muscle wasting and osteopenia as a myokine linking muscle to bone.

中文翻译：

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Dkk2 在雄激素缺乏小鼠肌肉/骨骼相互作用中的作用

已知雄激素缺乏会导致骨质疏松症和肌肉减少症。Myokines是骨骼肌分泌的体液因子，最近作为与肌肉和骨骼相互作用相关的关键因素而受到关注。Dickkopf (Dkk) 2 被称为经典 Wnt/β-catenin 信号传导的抑制剂，而 Wnt/β-catenin 信号传导对于维持肌肉和骨骼至关重要。因此，本研究旨在调查 Dkk2 在雄激素缺陷型睾丸切除术 (ORX) 小鼠肌肉和骨骼改变中的作用。ORX 显着增强小鼠比目鱼肌中的 Dkk2 mRNA 水平，但不增强其他 Dkks 和分泌的卷曲相关蛋白。此外，ORX 增强了小鼠胫骨组织、白色脂肪组织和肝脏中的血清 Dkk2 水平，但不增强 Dkk2 mRNA 水平。在简单回归分析中，血清 Dkk2 水平与实验中使用的小鼠胫骨骨小梁密度呈负相关。在体外实验中，睾酮抑制了小鼠肌肉 C2C12 细胞中的 Dkk2 mRNA 水平。总之，我们发现雄激素缺乏会增强小鼠肌肉中 Dkk2 的表达和分泌。Dkk2 可能与雄激素缺乏引起的肌肉萎缩和骨质减少有关，因为它是一种将肌肉与骨骼联系起来的肌因子。